Patient motion during magnetic resonance imaging (MRI) significantly limits our ability to produce high quality images, which is especially problematic in imaging young children unable to respond well (or at all) to verbal instructions and unable to remain still in the scanner. The images generated under these conditions are typically filled with artifacts and the data is therefore of little or no diagnostic value. In an efort to obtain useful images, sedation is routinely used in children < 8, but it is very expensive to administer and is not without potential side effects, some of which can be life-threatening. The research proposed under this application to the NIH provides a highly innovative solution to the following problem: Most young children are unable to remain motion-free long enough for existing motion measurement and correction approaches to produce diagnostically useful images with MRI. To overcome the persistent difficulties associated with imaging young children, we will develop motion-robust MRI that will 1) make trackerless motion measurements more rapidly and without patient-specific training; 2) use a novel combination of image acquisition techniques to make more efficient use of motion-free data; 3) obviate the need for sedation or anesthesia and thereby risks of mortality and morbidity associated with their use; and 4) achieve significantly lower overall costs, per patient and per scan. The computationally-driven technology developed under this proposal, motion-robust MRI, will be easily deployed in clinical settings with widely-available, standard MRI hardware; it will be simple to configure and calibrate; and it will generate images of superior resolution and diagnostic quality. To these ambitious ends, we will undertake the following Specific Aims over the 5-year period of requested support: 1) to develop, apply and evaluate real-time MRI motion measurement techniques; 2) to develop, apply and evaluate 2D/3D image reconstruction for retrospective motion correction; 3) to develop, apply, and evaluate prospective motion correction strategies utilizing motion measurements in real time; and 4) to apply and evaluate motion compensation techniques for imaging of 4-7-year-old patients. Given the fact that a significant number of children undergo MRI before age 18, and given the fact that MRI offers unrivaled diagnostic and prognostic capabilities without the potentially harmful effects of ionizing radiation associated with other modalities (e.g., x- ray, CT); the demand for improved motion compensation strategies for pediatric MRI has never been greater. This highly innovative imaging approach is therefore expected not only to create a new reference standard by which young children in particular are evaluated, diagnosed and monitored with MRI; it is also expected to have rapid translational impact for the countless pediatric diseases and disorders presently evaluated by MRI.